Field of the Invention
The present invention relates to the use of 1α,25-Dihydroxyvitamin D3-3β-bromoacetate (AMPI-109) for treatment of triple negative (TN, also called basal-like (BL)) breast cancer.
Description of the Related Art
Breast cancer is a heterogeneous disease exhibiting diverse biological characteristics and clinical responses. Gene expression profiling has defined genetic signatures corresponding to at least five distinct molecular subtypes of breast cancer including an aggressive form known as TN breast cancer.
There are three molecules that have been identified to promote many breast cancers: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). By definition, TN breast cancer fails to express these three molecules. Although TN breast cancer represents a relatively small percentage of all breast cancers (˜20%), it is typically high grade (poorly differentiated) and rapidly progressive, with a higher risk of relapse and lower survival than other subtypes of breast cancer. Therefore, TN breast cancer is associated with a disproportionate number of deaths. Additionally, for unknown reasons, TN breast cancer is often diagnosed in younger women and women of African-American descent.
Current clinical approaches for breast cancer typically include agents that target the three molecules identified to promote many breast cancers, such as endocrine therapies and the monoclonal antibody trastuzumab targeting HER2. Because TN breast cancer is defined as absence of these targets, conventional cytotoxic chemotherapy is currently the mainstay systemic treatment for patients with TN breast cancer. However, conventional systemic treatments are limited by poor therapeutic response, high toxicity, and the development of resistance. Although new approaches in the treatment of TN breast cancer such as targeting DNA repair with PARP inhibitors have emerged, there have been relatively fewer therapeutic advances in TN breast cancer when compared to other subtypes of the disease. Thus, there is a pressing need for targeted approaches toward the treatment of TN breast cancer.
In view of these problems, an object of the present invention is to develop an effective method for treating TN breast cancer. Another object is to develop a method targeting TN breast cancer cells of various molecular subtypes with little or no effect on normal cells. These and other objects have been achieved according to the present invention.